Intelligent therapy recommendation algorithim and method of using the same

ABSTRACT

An algorithm and method of making intelligent therapy recommendations for insulin pump parameters is described. The pump parameters include basal rates, carbohydrate-to-insulin ratios (CIR), and insulin sensitivity factors (ISF). A determination of whether a therapy recommendation should be made is based on comparing an updated recommended change with a threshold. The updated recommended change to the pump parameter is made based on a previous recommended change to the pump parameter and the difference between a current blood glucose value and a targeted blood glucose level. The algorithm and method confirms the therapy recommendation is within safety parameters before displaying the therapy recommendation.

RELATED APPLICATIONS

This application is a continuation application of U.S. patentapplication Ser No. 11/470,585 filed Sep. 6, 2006, which is hereinincorporated by reference.

FIELD OF THE INVENTION

The present invention relates to diabetes management, and in particularto adjusting insulin pump parameters using blood glucose information.

BACKGROUND OF THE INVENTION

The pancreas of a normal healthy person produces and releases insulininto the blood stream in response to elevated blood plasma glucoselevels. Beta cells β-cells), which reside in the pancreas, produce andsecrete the insulin into the blood stream, as it is needed. If β-cellsbecome incapacitated or die, a condition known as Type I diabetesmellitus (or in some cases if β-cells produce insufficient quantities ofinsulin, Type II diabetes), then insulin must be provided to the bodyfrom another source.

Traditionally, insulin has been injected with a syringe. More recently,use of infusion pump therapy has been increasing, especially fordelivering insulin for diabetics. For example, external infusion pumpsare worn on a belt, in a pocket, or the like, and deliver insulin intothe body via an infusion tube with a percutaneous needle or a cannulaplaced in the subcutaneous tissue. As of 1995, less than 5% of Type Idiabetics in the United States were using pump therapy, but presentlyover 25% of the more than 1.12 million Type I diabetics in the U.S. areusing infusion pump therapy. Although the infusion pump has improved theway insulin has been delivered, the infusion pump is limited in itsability to replicate all of the functions of the pancreas. Specifically,the infusion pump is still limited to delivering insulin based on userinputted commands and parameters and therefore there is a need toimprove the pump to better simulate a pancreas based on current glucosevalues.

SUMMARY OF THE DISCLOSURE

The present invention relates to an algorithm and method ofautomatically making a therapy recommendation for an insulin pumpparameter based on current blood glucose values and inputted targetedblood glucose levels. The pump parameters include basal rates,carbohydrate-to-insulin ratios (CIR), and insulin sensitivity factors(ISF). The preferred embodiments update a recommended change to the pumpparameter based on a previous recommended change to the pump parameterand the difference between the blood glucose value and a target bloodglucose level. The updated recommended change is compared to a thresholdvalue, and a therapy recommendation is derived if the absolute value ofthe recommended change exceeds that threshold value. In addition, thealgorithm confirms the therapy recommendation is within safetyparameters before displaying the therapy recommendation. In preferredembodiments, the therapy recommendation is considered to be withinsafety parameters if the blood glucose value is relatively consistentwith the blood glucose history. In still further preferred embodiments,the determination of whether blood glucose value is relativelyconsistent is determined by a moving standard deviation analysis.

In preferred embodiments, the blood glucose values are obtained by acontinuous glucose monitor. However, in alternative embodiments, theblood glucose value can be obtained by a glucose strip meter. Still infurther embodiments, various safety parameters are implemented. Inpreferred embodiments, limits on the therapy recommendation to aparticular maximum value are implemented in certain situations. In stillfurther embodiments, limits to an absolute maximum or absolute minimumvalue for the pump parameter can be implemented.

BRIEF DESCRIPTION OF THE DRAWINGS

A detailed description of embodiments of the invention will be made withreference to the accompanying drawings, wherein like numerals designatecorresponding parts in the several figures.

FIG. 1 is a flow chart illustrating the intelligent therapyrecommendation algorithm for basal rates in accordance with thepreferred embodiments of the present invention;

FIG. 2 is a flow chart illustrating the intelligent therapyrecommendation algorithm for carbohydrate to insulin ratio in accordancewith the preferred embodiments of the present invention;

FIG. 3 is a flow chart illustrating the intelligent therapyrecommendation algorithm for insulin sensitivity factor in accordancewith the preferred embodiments of the present invention; and

FIG. 4 is an example of a basal rate profile broken up into three hourintervals in accordance with the preferred embodiments of the presentinvention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

An insulin pump is designed to mimic the insulin delivery of a normalpancreas. To do so, an insulin pump delivers steady amounts of insulinthroughout a day known as a basal rate. The basal rate on an insulinpump delivers the amount of insulin needed in the fasting state tomaintain target glucose levels. The basal rate insulin is intended toaccount for the baseline insulin needs of the body, and makes upapproximately fifty percent of the body's total daily insulinrequirements. Thus, similar to the pancreas, the insulin pump deliversbasal rate insulin continuously over the twenty-four hours in the day.The insulin pump can be set to provide one or more different ratesduring different time intervals of the day. These different basal ratesat various time intervals during the day usually depend on a patient'slifestyle and insulin requirements. For example, many insulin pump usersrequire a lower basal rate overnight while sleeping and a higher basalrate during the day, or users might want to lower the basal rate duringthe time of the day when they regularly exercise.

A bolus is an extra amount of insulin taken to cover a rise in bloodglucose, often related to a meal or snack. Whereas a basal rate providescontinuously pumped small quantities of insulin over a long period oftime, a bolus provides a relatively large amount of insulin over afairly short period of time. Most boluses can be broadly put into twocategories: meal boluses and correction boluses. A meal bolus is theinsulin needed to control the expected rise in glucose levels due to ameal. A correction bolus is the insulin used to control unexpected highsin glucose levels. Often a correction bolus is given at the same time asa meal bolus because patients often notice unexpected highs in glucoselevels when preparing to deliver a meal bolus related to a meal.

Current insulin pumps can make bolus recommendations to the user. Anexample of a pump with a bolus estimator can be found in U.S. Pat. No.6,554,798, which is incorporated by reference herein in its entirety.The bolus estimator uses three values that must be preprogrammed toperform the necessary calculations in suggesting a bolus amount. Inalternative embodiments, more or fewer values may be needed or used. Theinputted values needed to be stored for the bolus estimator are:

Target Blood Glucose (Target), which is the target blood glucose (BG)that the user would like to achieve and maintain. Specifically, a targetblood glucose value is typically between 70-120 mg/dL for preprandialBG, and 100-150 mg/dL for postprandial BG.

Insulin Sensitivity Factor (ISF), which is a value that reflects how farthe user's blood glucose drops in milligrams per deciliter (mg/dl) whenone unit of insulin is taken. An example of an ISF value is 1 Unit for adrop of 50 mg/dl, although ISF values will differ from user to user.

Carbohydrate-to-Insulin Ratio (CIR), which is a value that reflects theamount of carbohydrates that are covered by one unit of insulin. Anexample of a CIR is 1 Unit of insulin for 15 grams of carbohydrates.Similarly, CIR values will differ from user to user.

After the above values are set in the memory of the insulin pump, thebolus estimator will suggest a bolus based on the entry of the estimatedcarbohydrate intake and current and target blood glucose (BG) levels.Preferred embodiments use the following equation:

${Bolus} = {\frac{\left( {{CurrentBG} - {TargetBG}} \right)}{I\; S\; F} + \frac{{Carbohydrates}\;{ToBeConsumed}}{C\; I\; R}}$If the user wishes the insulin pump to suggest a bolus for the estimatedcarbohydrate intake only, then the only value they need to program isfor the Carbohydrate Ratio, and the BG portion of the equation will beignored. In alternative embodiments, variations or different equationsmay be used.

One drawback is that currently the pump parameters like ISF, CIR, andbasal rates must be consistently and carefully monitored over a periodof time by the diabetic individual or physician so adjustments can bemade to help achieve and maintain the patient's target glucose level.For example, if fasting morning glucose is systematically higher thanthe target glucose level set by a health care provider or the diabeticindividual himself then the overnight basal rate must be adjusted. Inaddition, even after the pump parameters are set, a patient's body orbehavior pattern can change such that additional changes to the pumpparameters are needed. These changes require a great deal of recordkeeping and analysis to determine how much a parameter should bechanged. The difficulty in making these changes results in slowimplementation of making any changes to these pump parameters. Thesemodifications are even more difficult when the blood glucose readingsare only derived from finger stick measurements. It is often difficultand uncomfortable during this trial-and-error process for patients toconsistently monitor their blood glucose over a period of time and thenanalyze the pattern of those glucose levels. For example, a commonprocedure for currently adjusting basal rates is for a patient to testblood glucose levels with finger sticks at eight different times of theday including one in the middle of the night at 3 a.m. Adjustments aremade to the basal rate and then the procedure is repeated every daywhile making adjustments until blood glucose values no longer fluctuategreatly.

Blood glucose monitors, such as the blood glucose monitor described inU.S. Pat. No. 6,809,653, which is incorporated herein in its entirety,have improved many aspects of monitoring blood glucose levels withoutthe need for as many finger sticks, and giving a continuous glucose datathat can give a better picture of exactly how the glucose levels changethroughout the day. However, the data produced by the blood glucosemonitors have been independently used in conjunction with the deliveryof insulin using the infusion pump. There has always been a need for anintermediary such as a physician or the user themselves to act upon theblood glucose data and determine the need for changes to pumpparameters. The present invention provides an improved method formonitoring and adjusting insulin pump parameters using blood glucoseinformation obtained either through a glucose meter or a continuousglucose monitor.

According to an embodiment of the invention, an algorithm providesintelligent therapy recommendations for various pump therapy parametersto help patients more easily adjust those parameters to achieve andmaintain a target blood glucose level. The algorithm automaticallyrecommends adjustments to insulin pump parameters based on thedifference between a glycemic target and actual glucose measurements.

In the preferred embodiments, the algorithms are incorporated in aninsulin infusion pump that is able to receive signals from a glucosemonitor, an arrangement seen in the MiniMed Paradigm® Real Time InsulinPump and Continuous Glucose Monitoring System, which is incorporatedherein by reference in its entirety. In the preferred embodiments, thealgorithms are stored in the infusion pump's firmware, but can be storedin a separate software routine in the pump's ROM memory. In addition,the infusion pump controller is able to run the algorithms to performthe necessary steps to provide intelligent therapy recommendations forvarious pump therapy parameters. Alternatively, these algorithms can berun on a separate device such as a PDA, smart phone, computer, or thelike. In further alternative embodiments, the algorithms can be run onthe continuous glucose monitor or combination glucose monitor/infusionpump device or peripheral controller. In preferred embodiments, theintelligent therapy recommendations are displayed on the insulin pump,whether the recommendations themselves were calculated by the pumpcontroller or sent from another device either by cable or wirelessmeans. However, in alternative embodiments, the therapy recommendationscan also be given on any associated device such as a glucose monitordisplay, a handheld PDA or smartphone, a computer, etc.

Basal Rate

FIG. 1 describes an algorithm used to make adjustment recommendations toa basal rate in accordance with the preferred embodiments of the presentinvention. The algorithm of FIG. 1 can be used for both overnight basalrates and daytime basal rates. The algorithm begins at block 100. Block110 is used to apply the algorithm to the current day N, and the basalrate interval T is set to 0. Each day can be broken up into T number ofbasal rate intervals where the blood glucose level is recorded at theend of each of the intervals. In the preferred embodiments, the intervalis set to three hours so the glucose values are checked at the end ofevery three-hour interval throughout the day. For example, one basalrate interval T might be from 3 a.m. to 6 a.m. so the basal rate forthat interval will be adapted based on the glucose value at 6 a.m., andthe next interval will be from 6 a.m. to 9 a.m. where the glucose valueat 9 a.m. is used. An example of a basal rate profile broken up intothree hour intervals is seen in FIG. 4, where T is represents intervals1-8. As seen in FIG. 4, a basal rate profile can have various basalrates throughout the day, and the basal rates do not necessarily changeat each interval. Based on the running of the algorithm in FIG. 1,adjustments to the specific basal rates can be made for each timeinterval. One of skill in the art will appreciate that these intervalscan be started at anytime to match the user's schedule and intervals canbe greater or less than 3 hours in length. Potentially, the basal rateinterval can be as short as the minimum programmable basal rate intervalby an insulin pump (e.g. every 30 minutes on a MiniMed Paradigm® Pump)or have a maximum of having one single interval of 24 hours. Block 120is used to apply the algorithm to each basal rate interval T during dayN. The algorithm at block 130 then determines if there was a meal orcorrection bolus during the basal rate interval T. A meal or correctionbolus changes glucose levels unrelated to the basal rate, and so thealgorithm proceeds to the next interval because the meal or correctionbolus interferes with the analysis required for basal rate calculation.Referring back to block 130, if there was a meal or correction bolusduring interval T, the algorithm checks to see if T was the lastinterval of the day at block 180 and proceeds to the next interval T+1at block 120 to compare the next time interval. If T was the lastinterval of the day, then the algorithm moves to the next day at block110.

If there was no meal or correction bolus, then at block 140 arecommended change in basal rate is calculated based on the bloodglucose value at the end of the selected basal rate interval. In ourpreferred embodiment this step uses an error integration equation:ΔI _(B) _(T) ^(N) =ΔI _(B) _(T) ^(N−1) +K _(I)·(BG _(T)−Target)The first step in the error integration equation is to subtract thetarget glucose level (Target) from the actual glucose level (BG_(T)) atthe end of the basal rate interval T. The difference between thosevalues is then multiplied by a constant (K_(I)) which is an integralgain coefficient. It determines how fast the algorithm will respond to aglucose concentration over or under the target glucose level. K_(I) islikely linked to the total insulin requirements of the patient as wellas age, gender, and other patient specific parameters, and can beadjusted employing Bayesian statistics once studies of insulin deliveryin various segments of the population are performed. K_(I) may alsodiffer depending on the prevailing glucose level (e.g., K_(I) may behigher for adjustments to hypoglycemia than hyperglycemia). The resultof the multiplication of K_(I) and the blood glucose difference is knownas the scaled error. This scaled error is then added to the last knownproposed change for that particular basal rate interval (ΔI_(B) _(T)^(N−1)) resulting in the new proposed change to the basal rate for thattime interval (ΔI_(B) _(T) ^(N)). For example, if the basal rate for theinterval 3 a.m. to 6 a.m. on Day 70 was being analyzed then the BG_(T)would be the glucose value at 6 a.m. Next, the scaled error from the 3a.m. to 6 a.m. basal rate interval of Day 70 would be added to therecommended change from the 3 a.m. to 6 a.m. basal rate interval of Day69.

At block 150, the algorithm compares the absolute value of therecommended change calculated at block 140 to a predefined threshold,typically 0.05 or 0.1 U/h. If the absolute value of the recommendedchange is less than the predefined threshold, then the algorithm goes toblock 125 to move on to the next interval or the next day. However, ifthe recommended change is greater than the predefined threshold, thenthe recommendation is evaluated for safety at block 160. In preferredembodiments the safety review of block 160 makes sure that the glucosehistory is not too variable for a therapy recommendation to be made. Atherapy recommendation should only be made if there is a consistentpattern in blood glucose levels to provide a certain level of confidencein the proposed therapy recommendation. In the preferred embodiments,the algorithm determines the variability of the glucose history by usingthe moving standard deviation, which is the standard deviation of acluster of the most recent data. The moving standard deviation(mSTD(BG)) is compared against the difference between the averageglucose value (BG_(avg)) and the targeted blood glucose (Target). If theglucose history is too variable for a therapy recommendation to be made(e.g. mSTD(BG)>BG_(avg)−Target), then no therapy recommendation is madeto the user and the logic proceeds to block 180, where the recommendedchange is reset (e.g. ΔI_(B) _(T) ^(N) is reset to zero). The algorithmthen proceeds from block 180 to block 125 to determine if there isanother basal rate interval that day, and then analyzes the next basalrate interval or moves to the next day. In alternative embodiments, thesafety check is only applied for increases in the basal rate because theimmediate risks of hypoglycemia are much greater than hyperglycemia.Hypoglycemia can cause a person to pass out in 15 or 30 minutes while ittakes hours for the severe effects of hyperglycemia to become evidentand cause problems.

On the other hand, if the glucose history is not too variable for atherapy recommendation to be made at block 160 (e.g.mSTD(BG)<BG_(avg)−Target), then the algorithm proceeds to block 170where a therapy recommendation is made to the user. Although the therapyrecommendation is tied to the final recommended change calculation thatexceeds the threshold, the two values are not necessarily equal. Forexample, in one embodiment, the therapy recommendation can be preset toa particular value (e.g. 0.1 Units/hour) such that the therapyrecommendation is made when the recommended change exceeds the thresholdregardless of what the recommended change value is finally derived. Thetherapy recommendation can be displayed on the infusion pump displayand/or combined with different alarms such as vibration, audio, etc. Inthe preferred embodiments, if the therapy recommendation is for anincrease in the basal rate, the therapy recommendation made to the userin block 170 is capped at a particular maximum as an additional safetyprecaution. In preferred embodiments, the maximum therapy recommendationincrease in basal rate is set at 0.1 Unit/hour for an overnight basalrate and 0.2 Unit/hour for daytime basal rate. In alternativeembodiments, the maximum therapy recommendation can be set at a higheror lower value. Also, in alternative embodiments, limits on largedecreases in the basal rate can be implemented or upper and lowerboundaries for the overall basal rate in addition to limits on the sizeof changes to the basal rate can be used.

Additionally, in preferred embodiments, the therapy recommendation isalways rounded to the nearest 0.1 or 0.05 U/h because this is thesmallest incremental change currently possible for the MiniMed Paradigm®pumps and other insulin pumps. In alternative embodiments, the therapyrecommendation may be rounded to the nearest 0.025 U/h as future pumpsallow for smaller incremental changes. After a therapy recommendation isor is not made to the user at block 170, the algorithm resets therecommended change (e.g. ΔI_(B) _(T) ^(N) is set to zero). The algorithmdoes not depend on the user accepting or rejecting the therapyrecommendation since the recommended change is reset regardless. Thealgorithm then advances to block 125 to determine if there is anotherbasal rate interval that day. If the basal rate interval at block 125 isnot the last one of the day then the algorithm advances to the nextbasal rate interval of the day at block 120. If it is the last basalrate interval of the day then the algorithm proceeds to the next day atblock 110 where the process begins again.

Although the above description was applied to a single daily basal rateprofile (or “basal delivery pattern” or “personal delivery pattern” asused synonymously in the industry), in alternative embodiments, thealgorithms can be applied to situations where the insulin pump hasmultiple basal rate profiles. Specifically, the algorithm can be used tomake recommended changes to basal rate profile A by comparing basal rateprofile A with only previous basal rate profile A, and makingrecommended changes to basal rate profile B by comparing basal rateprofile B with only previous basal rate profile B, etc.

Carbohydrate-to-Insulin Ratio (CIR)

FIG. 2 describes an algorithm used to make adjustment recommendations toa carbohydrate-to-insulin ratio (CIR) in accordance with the preferredembodiments of the present invention. The algorithm begins at block 200,where the algorithm reviews the postprandial blood glucose values aftereach meal before making or not making a recommended change to the CIR.Block 210 sets the counter variable so that the algorithm applies to thecurrent meal N, In preferred embodiments, the algorithm at block 220finds the glucose level two hours after meal N. Theoretically, two hoursis the ideal time to measure the postprandial blood glucose value, but alonger or shorter time can be used. After the postprandial blood glucosevalue for meal N is retrieved, the algorithm at block 230 considerswhether another meal was consumed during the two hours after meal N. Inthe preferred embodiments, the algorithm searches for meal or errorcodes within 2 hours after the last meal event, but this interval can begreater or less than 2 hours in length. A meal or error code changesglucose levels unrelated to the CIR, and so the algorithm proceeds tothe next meal because the meal or error code interferes with theanalysis required for CIR calculation. If there was a meal or errorcode, the algorithm skips the calculation for meal N and goes to block210 to consider the next meal or move to the next day. If no meal wasconsumed within two hours of the last meal, the algorithm proceeds toblock 240.

At block 240 a recommended change in the CIR is calculated based on thepostprandial blood glucose value. In our preferred embodiment this stepuses an error integration equation:ΔCIR^(N)=ΔCIR^(N−1) −K _(I) _(CIR) ·(BG_(2h) _(_) _(POST)−Target)The first step in the error integration equation is to subtract thetarget glucose level (Target) from the actual glucose level (BG_(2h)_(_) _(POST)) two hours after the meal. The difference between thosevalues is then multiplied by a constant (K_(I) _(CIR) ) which is theintegral gain coefficient for CIR. K_(I) _(CIR) determines how fast thealgorithm will respond to a glucose concentration over or under thetarget glucose level. K_(I) _(CIR) is likely linked to the total insulinrequirements of the patient as well as age, gender, and other patientspecific parameters, and can be adjusted employing Bayesian statisticsonce studies of insulin delivery in various segments of the populationare performed. K_(I) _(CIR) may also differ depending on the prevailingglucose level (e.g., K_(I) _(CIR) may be higher for adjustments tohypoglycemia than hyperglycemia). The result of the multiplication ofK_(I) _(CIR) and the blood glucose difference is known as the scalederror. This scaled error is then subtracted from the last known proposedchange for the CIR (ΔCIR^(N−1)) resulting in the new proposed change tothe CIR (ΔCIR^(N)).

At block 250, the algorithm compares the absolute value of therecommended change calculated at block 240 to a predefined threshold,typically 5 grams carbohydrates per unit of insulin. If the absolutevalue of the recommended change is less than the predefined threshold,than the algorithm goes to block 210 to move on to the next meal event.However, if the recommended change is greater than the predefinedthreshold, then the recommendation is evaluated for safety at block 260.In preferred embodiments, the safety review of block 260 makes sure thatthe glucose history is not too variable for a therapy recommendation tobe made. A therapy recommendation should only be made if there is aconsistent pattern in blood glucose levels to provide a certain level ofconfidence in the proposed therapy recommendation. In the preferredembodiments, the algorithm determines the variability of the glucosehistory by using the moving standard deviation, which is the standarddeviation of a cluster of the most recent data. The moving standarddeviation (mSTD(BG)) is compared against the difference between theaverage glucose value (BG_(avg)) and the targeted blood glucose(Target). If the glucose history is too variable for a therapyrecommendation to be made (e.g. mSTD(BG)>BG_(avg)−Target), then notherapy recommendation is made to the user and the logic proceeds toblock 280, where the recommended change is reset (e.g. ΔCIR^(N) is resetto zero). The algorithm then proceeds from block 280 to block 210 toanalyze the next meal. In alternative embodiments, the safety check isonly applied for decreases in CIR because the immediate risks ofhypoglycemia are much greater than hyperglycemia.

On the other hand, if the glucose history is not too variable for atherapy recommendation to be made at block 260 (e.g.mSTD(BG)<BG_(avg)−Target), then the algorithm proceeds to block 270where a therapy recommendation is made to the user. Again, the therapyrecommendation is not necessarily equal to the recommended change valuethat exceeds the threshold. The therapy recommendation can be displayedon the infusion pump display and/or combined with different alarms suchas vibration, audio, etc. In the preferred embodiments, if the therapyrecommendation is for a decrease in the CIR, the therapy recommendationmade to the user in block 270 is capped at a particular maximum as anadditional safety precaution. For example, the maximum cap could be setto not modify the current CIR by more than 10 carbohydrates for a Unitof insulin. In alternative embodiments, the maximum therapyrecommendation decrease can be set at a higher or lower value. Also inalternative embodiments, limits on large increases in the CIR can beimplemented or upper and lower boundaries for the overall CIR inaddition to limits on the size of therapy recommendations to the CIR canalso be used.

Additionally, in preferred embodiments, the therapy recommendation isalways rounded to the nearest whole number for CIR because this is thesmallest incremental change currently possible for the MiniMed Paradigm®pumps and other insulin pumps. After a therapy recommendation is or isnot made to the user at block 270, the algorithm resets the recommendedchange (e.g. ΔCIR^(N) is reset to zero). The algorithm does not dependon the user accepting or rejecting the therapy recommendation since therecommended change is reset regardless. The algorithm then proceeds tothe next meal at block 210.

Although the preferred embodiments describe an algorithm that updatesthe recommended change after each meal, alternative embodiments may usea loop structure to review every meal in one day before comparing therecommended change to the threshold. Thus, the recommended change willbe refined after each meal in a day to have the most last recommendedchange compared to the preset threshold. Alternative embodiments may usea loop structure for a specific meal only, i.e. breakfast, thus refiningthe recommended change in CIR for breakfast only. In still furtheralternative embodiments, the algorithm does not have to have to limitthe loop structure to a single day. For example, the algorithm canreview all the meals over one week before deciding whether to make arecommendation to the change in CIR, or the algorithm can runcontinuously until the threshold is passed.

Insulin Sensitivity Factor (ISF)

FIG. 3 describes an algorithm used to make adjustment recommendations tothe insulin sensitivity factor (ISF) in accordance with the preferredembodiments of the present invention. A correction bolus is defined inthis algorithm as a bolus to correct for high blood glucose values inisolation of any meal bolus. Therefore, if a bolus was taken for both ameal and to correct for high blood glucose at the same time, the boluswould not be used in this algorithm. The algorithm begins at block 300,where the algorithm reviews the blood glucose values after eachcorrection bolus before making or not making a recommended change to theISF. Block 310 sets the counter variable so that the algorithm appliesto the current correction bolus N. In preferred embodiments, thealgorithm at block 320 finds a correction bolus event N and checks theblood glucose value two hours after the correction bolus. The algorithmat block 330 then determines if there were any meals or error codesafter the correction bolus event N. In the preferred embodiments, thealgorithm searches for meal or error codes within 2 hours after thecorrection bolus event, but this interval can be greater or less than 2hours in length. A meal or error code changes glucose levels unrelatedto the ISF, and so the algorithm proceeds to the next correction bolusevent because the meal or error code interferes with the analysisrequired for ISF calculation.

If there was no meal or error code within two hours of the correctionbolus, then at block 340 a recommended change in ISF is calculated basedon the blood glucose value two hours after the correction bolus. In ourpreferred embodiment this step uses an error integration equation:ΔISF^(N)=ΔISF^(N−1) −K _(I) _(ISF) ·(BG_(2h) _(_) _(POST)−Target)The first step in the error integration equation is to subtract thetarget glucose level (Target) from the actual glucose level (BG_(2h)_(_) _(POST)) two hours after the correction bolus. The differencebetween those values is then multiplied by a constant (K_(I) _(ISF) )which is the integral gain coefficient for ISF. K_(I) _(ISF) determineshow fast the algorithm will respond to a glucose concentration over orunder the target glucose level. K_(I) _(ISF) is also linked to the totalinsulin requirements of the patient as well as age, gender, and otherpatient specific parameters, and can be adjusted employing Bayesianstatistics once studies of insulin delivery in various segments of thepopulation are performed. K_(I) _(ISF) may also differ depending on theprevailing glucose level (e.g., K_(I) _(ISF) may be higher foradjustments to hypoglycemia than hyperglycemia). The result of themultiplication of K_(I) _(ISF) and the blood glucose difference is knownas the scaled error. This scaled error is then subtracted from the lastknown proposed change for the ISF (ΔISF^(N−1)) resulting in the newproposed change to the ISF (ΔISF^(N)).

At block 350, the algorithm compares the absolute value of therecommended change calculated at block 340 to a predefined threshold,typically 5 mg/dl for a Unit of insulin. If the absolute value of therecommended change is less than the predefined threshold, then thealgorithm goes to block 310 to move on to the next correction bolusevent. However, if the absolute value of the recommended change isgreater than the predefined threshold, then the recommendation isevaluated for safety at block 360. In preferred embodiments, the safetyreview of block 360 makes sure that the glucose history is not toovariable for a therapy recommendation to be made. A therapyrecommendation should only be made if there is a consistent pattern inblood glucose levels to provide a certain level of confidence in theproposed therapy recommendation. In the preferred embodiments, thealgorithm determines the variability of the glucose history by using themoving standard deviation, which is the standard deviation of a clusterof the most recent data. The moving standard deviation (mSTD(BG)) iscompared against the difference between the average glucose value(BG_(avg)) and the targeted blood glucose (Target). If the glucosehistory is too variable for a therapy recommendation to be made (e.g.mSTD(BG)>BG_(avg)−Target), then no therapy recommendation is made to theuser and the logic proceeds to block 280, where the recommended changeis reset (e.g. ΔISF^(N) is reset to zero). The algorithm then proceedsfrom block 380 to block 310 to analyze the next correction bolus event.In alternative embodiments, the safety check is only applied fordecreases in ISF because the immediate risks of hypoglycemia are muchgreater than hyperglycemia.

On the other hand, if the glucose history is not too variable for atherapy recommendation to be made at block 360 (e.g.mSTD(BG)<BG_(avg)−Target), then the algorithm proceeds to block 370where the therapy recommendation is made to the user. Again, the therapyrecommendation is not necessarily equal to the recommended change valuethat exceeds the threshold. The therapy recommendation can be displayedon the infusion pump display and/or combined with different alarms suchas vibration, audio, etc. In the preferred embodiments, if the therapyrecommendation is for an decrease in the ISF, the therapy recommendationdecrease made to the user in block 370 is capped at a particular maximumas an additional safety precaution. For example, the maximum cap couldbe set to not modify the current ISF by more than 10 mg/dl for a Unit ofinsulin. In alternative embodiments, the maximum therapy recommendationdecrease can be set at a higher or lower value. Also, limits on largeincreases in the ISF can be implemented or upper and lower boundariesfor the overall ISF in addition to limits on the size of therapyrecommendations to the ISF can be used.

Additionally, in preferred embodiments, the therapy recommendation isalways rounded to the nearest whole number for ISF because this is thesmallest incremental change currently possible for the MiniMed Paradigm®pumps and other insulin pumps. After a therapy recommendation is made tothe user at block 370, the algorithm resets the recommended change (e.g.ΔISF^(N) is reset to zero). The algorithm does not depend on the useraccepting or rejecting the therapy recommendation since the recommendedchange is reset regardless. The algorithm then advances to the nextcorrection bolus event at block 310

Although the preferred embodiments describe an algorithm that updatesthe recommended change after each correction bolus event, alternativeembodiments may use a loop structure to review all the correctionboluses in one day before comparing the recommended change to thethreshold. Thus, the recommended change will be refined after eachcorrection bolus calculation such that the last recommended change isthen compared to the preset threshold. In still further alternativeembodiments, the algorithm does not have to have to limit the loopstructure to a single day. For example, the algorithm can review all thecorrection bolus events over one week before deciding whether to make arecommendation to the change in ISF, or be allowed to run continuouslyuntil the threshold is met.

Therefore, as described above, various modifications and alternativesare possible in implementing the present invention. Moreover, otheralternative embodiments are possible from the above description. Forexample, a modified error integration formula can be substituted for theerror integration formula described in the preferred embodiments. Onepossibility is to use the area under the glucose curve (AUC) rather thanthe actual glucose level (BG) at the end of interval T. For example, forpurposes of basal rate, the modified error integration formula can be asfollows:ΔI _(B) _(T) ^(N) =ΔI _(B) _(T) ^(N−1) +K _(I)*(AUC_(T)−Target)Additional steps and changes to the order of the algorithm can be madewhile still performing the key teachings of the present invention. Forexample, additional safety parameters can be applied as well as removedfrom the algorithm. In addition, in the case of concurrent algorithmrecommendations, Bayesian statistics might be applied to determine theorder of change in pump therapy parameters. So while the descriptionabove refers to particular embodiments of the present invention, it willbe understood that many modifications may be made without departing fromthe spirit thereof. The accompanying claims are intended to cover suchmodifications as would fall within the true scope and spirit of thepresent invention.

The presently disclosed embodiments are therefore to be considered inall respects as illustrative and not restrictive, the scope of theinvention being indicated by the appended claims, rather than theforegoing description, and all changes which come within the meaning andrange of equivalency of the claims are therefore intended to be embracedtherein.

What is claimed is:
 1. A method of automatically making a therapyrecommendation for adjusting a basal rate stored on an insulin pump, themethod comprising the steps of: obtaining a blood glucose value at theend of a time interval; determining if an intervening event occurredduring the time interval , wherein the intervening event changes theblood glucose value unrelated to the stored basal rate and therebyinterferes with recommending a change to the stored basal rate;recommending no change to the stored basal rate based on the bloodglucose value if the intervening event occurred during the timeinterval; updating a recommended change to the stored basal rate basedon a previous day recommended change to the stored basal rate duringthat interval and the difference between the blood glucose value and atarget blood glucose level if no intervening event occurred during thetime interval; comparing an absolute value of the updated recommendedchange to a predefined threshold value of the stored basal rate; makingno therapy recommendation if the updated recommended change does notexceed the threshold or the therapy recommendation is not within safetyparameters; making the therapy recommendation if the updated recommendedchange exceeds the threshold and the therapy recommendation is withinsafety parameters; and displaying the therapy recommendation to adjustthe stored basal rate.
 2. The method of claim 1, wherein the basal rateis an overnight basal rate.
 3. The method of claim 1, wherein the stepof recommending no change to the stored basal rate further comprises:skipping the blood glucose value if the intervening event includes ameal or a correction bolus during the time interval before the bloodglucose value was obtained.
 4. The method of claim 1, wherein the stepof confirming the therapy recommendation is within safety parameterscomprises: reviewing recent blood glucose history; and using a movingstandard deviation analysis on the recent blood glucose history toconfirm the blood glucose value is relatively consistent with the bloodglucose history.